This application requests support for continuation of a rigorous predoctoral Training Program that focuses on the molecular analysis of microbial pathogens. Experimental research training is the primary focus of this Program. A key and complementary component of the Training Plan is the requirement for PhD students to have exposure to problems in clinical medicine through participation in a seminar course and in clinical rounds. The training program is designed to provide students with the tools to become independent research scientists in academia or industry while in parallel providing a deep understanding of current problems in clinical infectious diseases. The Training Program is a track within the interdepartmental Graduate Program in Molecular Microbiology and draws faculty members from the Departments of Molecular Biology and Microbiology, Biochemistry, Medicine, Molecular Physiology and Pharmacology, and Pathology. All investigators have a common interest either in pathogenic microorganisms or in restriction of pathogens in cell or animal models. The varied research interests of the group include: a) bacterial pathogenesis, including the study of colonization, intracellular growth, toxin expression and development of tools to study microbial genes expressed during animal infections; b) viral pathogenesis and replication; c) viral persistence and oncogenesis; d) viral and bacterial evolution during disease; e) development of novel anti-parasitic and anti- fungal strategies; f) protein secretion and the analysis of yeast, parasite and bacterial surfaces; and g) regulation of gene expression and cell growth in microbial model systems; h) analysis of developmental stages in fungal pathogens; i) mouse models of innate immunity; j) microbial interaction with effectors of acquired immunity. The members of this Program use genetic and biochemical strategies to analyze microbial pathogens as well as animal infection models. This Program has a long history of having a strong collaborative spirit of learning and research among faculty and students. Recruitment and admission strategies have been highly successful, with an excellent minority recruitment program, as over 20% of the students are members of underrepresented minority groups. The overwhelming majority of the 175 Ph.D. graduates of the Department since 1964 are currently employed in research positions in academics and industry, with approximately 40% of the graduates who have finished postdoctoral training obtaining faculty positions. The Program is overseen by the Training Committee, a group of internationally recognized bacteriologists and virologists who participate in the graduate education of all trainees. The application is for five years of support for 5 predoctoral trainee positions per year. Trainees are chosen by a rigorous selection process and are supported for 2 years. PUBLIC HEALTH RELEVANCE: The goal is to give trainees who are intensely involved in laboratory research a complementary understanding of challenges involved in treating patients. One of the primary goals of our Program is to train PhD students to understand clinical infectious diseases while acquiring the basic research knowledge and tools they will need to investigate and solve these problems through hypothesis-driven research. Programs that ensure that scientists understand the clinical implications of their research and facilitate the movement of scientific discoveries to the bedside are greatly needed in this country.